Latest revision as of 23:34, 15 July 2024

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Section editor
	Eric I. Marks, MD Boston University Boston, MA, USA

3 regimens on this page 3 variants on this page

Are you looking for a regimen, but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: this page has regimens which are specific to pancreatic cancer that is BRCA-mutated. Please see the main pancreatic cancer page for other chemotherapy regimens.

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Pancreatic Adenocarcinoma.

Advanced or metastatic disease, first-line

Cisplatin & Gemcitabine (GC)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
O'Reilly et al. 2020 (MSKCC 12-045)	2014-2018	Randomized Phase 2 (C)	GC & Veliparib	Did not meet primary endpoint of RR

Selected inclusion criteria: germline BRCA1/2 or PALB2 mutation and previously untreated stage III-IV pancreatic adenocarcinoma. The addition of veliparib did not improve RR.

Biomarker eligibility criteria

Germline BRCA1/2 or PALB2+ mutation

Chemotherapy

Cisplatin (Platinol) 25 mg/m² IV once per day on days 3 & 10
Gemcitabine (Gemzar) 600 mg/m² IV over 30 minutes once per day on days 3 & 10

21-day cycles

References

MSKCC 12-045: O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen D. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 01;38:1378-1388. Epub 2020 Jan 24. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01585805

Maintenance after first-line therapy

Olaparib monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Golan et al. 2019 (POLO)	2015-2019	Phase 3 (E-RT-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 7.4 vs 3.8 mo (HR 0.53, 95% CI 0.35-0.82)

Selected inclusion criteria: germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy.

Biomarker eligibility criteria

Germline BRCA1 or BRCA2 mutation

Preceding treatment

First-line platinum-based chemotherapy for at least 16 weeks

Targeted therapy

Olaparib (Lynparza) 300 mg PO twice per day

Continued indefinitely

References

POLO: Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT02184195
1. HRQoL analysis: Hammel P, Kindler HL, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Joo S, Yoo HK, Patel N, Golan T; POLO Investigators. Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib. Ann Oncol. 2019 Dec 1;30(12):1959-1968. link to original article link to PMC article PubMed
2. Update: Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. link to original article link to PMC article PubMed

Metastatic disease, refractory

Olaparib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Kaufman et al. 2014 (Study 42)	2010-02-21 to 2012-07-31	Phase 2

Biomarker eligibility criteria

Germline BRCA1/2 mutations

Prior treatment criteria

Gemcitabine, with progression

Targeted therapy

Olaparib (Lynparza) 400 mg PO twice per day

Continued indefinitely

References

Study 42: Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01078662

Additional resources

@@ Line 3: / Line 3: @@
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-{{#lst:Section editor transclusions|giei}}
+{{#lst:Editorial board transclusions|giei}}
 {| class="wikitable" style="float:right; margin-right: 5px;"
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 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
-<big>'''Note: this page has regimens which are specific to pancreatic cancer that is BRCA-mutated. Please see the [[Pancreatic cancer|main pancreatic cancer]] page for other chemotherapy regimens.'''</big>
+''Are you looking for a regimen, but can't find it here? For placebo or observational studies in this condition, please visit [[Pancreatic cancer, BRCA-mutated - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' <br>
+'''Note: this page has regimens which are specific to pancreatic cancer that is BRCA-mutated. Please see the [[Pancreatic cancer|main pancreatic cancer]] page for other chemotherapy regimens.'''
 {{TOC limit|limit=3}}
+=Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
+==NCCN==
+*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455 NCCN Guidelines - Pancreatic Adenocarcinoma].''
 =Advanced or metastatic disease, first-line=
 ==Cisplatin & Gemcitabine (GC) {{#subobject:344hc7|Regimen=1}}==
@@ Line 25: / Line 30: @@
 |2014-2018
 | style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Veliparib_77|GC & Veliparib]]
+|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Veliparib_999|GC & Veliparib]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of RR
 |-
@@ Line 37: / Line 42: @@
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 3 & 10
-*[[Gemcitabine (Gemzar)]] 600 mg/m<sup>2</sup> IV once per day on days 3 & 10
+*[[Gemcitabine (Gemzar)]] 600 mg/m<sup>2</sup> IV over 30 minutes once per day on days 3 & 10
 '''21-day cycles'''
 </div></div>
 ===References===
-#'''MSKCC 12-045:''' O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen D. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline ''BRCA/PALB2'' Mutation. J Clin Oncol. 2020 May 01;38:1378-1388. [https://doi.org/10.1200/jco.19.02931 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7193749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31976786/ PubMed] NCT01585805
+#'''MSKCC 12-045:''' O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen D. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline ''BRCA/PALB2'' Mutation. J Clin Oncol. 2020 May 01;38:1378-1388. Epub 2020 Jan 24. [https://doi.org/10.1200/jco.19.02931 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7193749/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31976786/ PubMed] [https://clinicaltrials.gov/study/NCT01585805 NCT01585805]
 =Maintenance after first-line therapy=
 ==Olaparib monotherapy {{#subobject:388hc7|Regimen=1}}==
@@ Line 58: / Line 64: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ Golan et al. 2019 (POLO)]
-{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-208-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
 |-
-|}
+|} -->
 |2015-2019
 | style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Placebo|Placebo]]
+|[[Pancreatic_cancer,_BRCA-mutated_-_null_regimens#Placebo|Placebo]]
 | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7.4 vs 3.8 mo<br>(HR 0.53, 95% CI 0.35-0.82)
 |-
@@ Line 75: / Line 81: @@
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[Regimen_classes#Platinum-based_regimen|Platinum-based chemotherapy]] for at least 16 weeks
+*First-line [[Regimen_classes#Platinum-based_regimen|platinum-based chemotherapy]] for at least 16 weeks
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
@@ Line 83: / Line 89: @@
 </div></div>
 ===References===
-#'''POLO:''' Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903387 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963/ PubMed] NCT02184195
+#'''POLO:''' Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903387 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963/ PubMed] [https://clinicaltrials.gov/study/NCT02184195 NCT02184195]
 ##'''HRQoL analysis:''' Hammel P, Kindler HL, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Joo S, Yoo HK, Patel N, Golan T; POLO Investigators. Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib. Ann Oncol. 2019 Dec 1;30(12):1959-1968. [https://doi.org/10.1093/annonc/mdz406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938600/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31562758/ PubMed]
-##'''Update:''' Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. [https://doi.org/10.1200/jco.21.01604 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35834777/ PubMed]
+##'''Update:''' Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. [https://doi.org/10.1200/jco.21.01604 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476841/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35834777/ PubMed]
-==Placebo==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ Golan et al. 2019 (POLO)]
-|2015-2019
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Olaparib_monotherapy|Olaparib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[Regimen_classes#Platinum-based_regimen|Platinum-based chemotherapy]] for at least 16 weeks
-</div></div>
-===References===
-#'''POLO:''' Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903387 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963/ PubMed] NCT02184195
-##'''HRQoL analysis:''' Hammel P, Kindler HL, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Joo S, Yoo HK, Patel N, Golan T; POLO Investigators. Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib. Ann Oncol. 2019 Dec 1;30(12):1959-1968. [https://doi.org/10.1093/annonc/mdz406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938600/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31562758/ PubMed]
-##'''Update:''' Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. [https://doi.org/10.1200/jco.21.01604 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35834777/ PubMed]
 =Metastatic disease, refractory=
 ==Olaparib monotherapy {{#subobject:0c2eb3|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:21eb78|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)]
+|2010-02-21 to 2012-07-31
 | style="background-color:#91cf61" |Phase 2
 |-
@@ Line 137: / Line 120: @@
 ===References===
 <!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
-#'''Study 42:''' Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366685 PubMed] NCT01078662
+#'''Study 42:''' Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366685/ PubMed] [https://clinicaltrials.gov/study/NCT01078662 NCT01078662]
 =Additional resources=
 *[https://oncomx.org/searchview/?gene=BRCA1 OncoMX -- BRCA1]

Difference between revisions of "Pancreatic cancer, BRCA-mutated"

Latest revision as of 23:34, 15 July 2024

Contents

Guidelines

NCCN

Advanced or metastatic disease, first-line

Cisplatin & Gemcitabine (GC)

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Maintenance after first-line therapy

Olaparib monotherapy

Regimen

Biomarker eligibility criteria

Preceding treatment

Targeted therapy

References

Metastatic disease, refractory

Olaparib monotherapy

Regimen

Biomarker eligibility criteria

Prior treatment criteria

Targeted therapy

References

Additional resources

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